Researcher studies mechanism of s-looping to prevent heart abnormalities in infants

Ashok Ramasubramanian, assistant professor of mechanical engineering at Union College, believes that the study of the tiny tubes that make up the embryonic heart offers new hope to babies born with heart abnormalities. So, he's looking to chicken embryos for clues. Ramasubramanian's findings were published in the April 2013 issue of Developmental Dynamics.

A pair of atria, an aorta, a tricuspid valve, a pulmonary vein, the superior vena cava - all this - the human heart - is just a minuscule cylinder at first.

"Initially, the embryonic heart forms as a straight tube, like a garden hose," said Ramasubramanian. "To become the complex mature organ, it twists and bends as a baby grows through a process called looping. Certain genes change its shape, but there are also forces."

This is how it works: Consider that you go to California and your head is a gene. If your head falls off, you won't go. But your head is not all that gets you there. Other forces, like a plane, are involved.

In the same way, the primitive heart has no intrinsic ability to start the important s-looping process, which moves the primitive ventricle to its definitive position above the atrium. It takes external forces to get the process moving.

"It's these - the mechanisms of gene action - we study to see how the heart actually twists," said Ramasubramanian.

During this critical period, occurring in the first 48 to 56 hours of a chick's 21-day incubation, groundwork is laid for the basic cardiac shape - two atria at the top and two ventricles at the bottom. Previous studies established that cervical flexure - the bend in the neural tube that connects the brain to spinal cord - played a key role in the process. Ramasubramanian's study took it a step further, suggesting that forces applied by 'cardiac jelly' or the membranes on the sides of the heart - the splanchnopleure (SPL) - also cannot be ignored during early s-looping.

"As far as we know, we are the first group to develop a three-dimensional computer model for early cardiac s-looping that includes both the myocardium and the cardiac jelly," said Ramasubramanian. "By using a specific combination of SPL pressure and the heart tube, we were able to manipulate the s-looping process into bending in just the right way."

So what does it mean for babies with heart abnormalities?

"In many cases, we can't treat in utero, partly because cardiac development is poorly understood," Ramasubramanian said. "By understanding the biophysical mechanisms that drive the s-looping process, we can better pinpoint how and when we might be able to influence heart development. And a better understanding can potentially save more lives."